MTTP variants and body mass index, waist circumference and serum cholesterol level: Association analyses in 7582 participants of the KORA study cohort.
The microsomal triglyceride transfer protein (MTTP) is a key regulator in the assembly and secretion of chylomicrons and very low density lipoprotein (VLDL) in the intestine and in liver. Associations between MTTP variants and traits of the metabolic syndrome are carried out in relatively small cohorts and are not consistent. We analysed MTTP polymorphisms in 7582 participants of the KORA study cohort. Seven htSNPs covering a 52kb region of the MTTP locus and two cSNPs (I128T, H297Q) were selected. A MTTP haplotype containing the minor allele of H297Q showed a significant decrease of -0.636 (95% CI: -1.226, -0.046; p=0.035) BMI units in females but not in males. In comparison to homozygous H-carriers for the major allele of the MTTP H297Q polymorphism, homozygous Q297Q carriers showed a significant decrease in BMI of -0.425B MI units (95% CI: -0.74, -0.12; p=0.007), in waist circumference of -0.990 cm (95% CI: 1.74, -0.24; p=0.01) and in total cholesterol of -0.039 mmol/l (95% CI: -0.07, 0; p=0.03). Heterozygous Q-carriers displayed a reduction in BMI of -0.183 BMI unit (95% CI: -0.33, -0.04; p=0.012), in waist circumference of -0.45 cm (95% CI: 0.8, -0.1; p=0.01) and in total cholesterol of -0.103 mmol/l (95% CI: -0.18, -0.03; p=0.01). Gender stratified statistics revealed a significant reduction of -0.657 BMI units (95% CI: -1.14, -0.18; p=0.007), -1.437 cm waist circumference (95% CI: -2.55, -0.32; p=0.01) and -0.052 mmol/l total cholesterol (95% CI: -0.1, -0.01; p=0.03) for females homozygous for the Q297Q polymorphism. Females carrying the Q-allele showed a decrease of -0.259 BMI unit (95% CI: -0.48, -0.04; p=0.023), -0.662 cm waist circumference (95% CI: -1.18, -0.14; p=0.01) and -0.111 mmol/l total cholesterol (95% CI: -0.21, -0.01; p=0.03). Our association analysis in a large population based study cohort provides evidence that the minor allele of the MTTP H297Q polymorphism is associated with lower BMI, waist circumference and total cholesterol in females but not in males.
Böhme
Mike
M
Institute of Human Nutrition and Food Science, Molecular Nutrition, Christian-Albrecht-University, Heinrich-Hecht-Platz 10, 24118 Kiel, Germany.
Grallert
Harald
H
Fischer
Alexandra
A
Gieger
Christian
C
Nitz
Inke
I
Heid
Iris
I
Kohl
Christine
C
Wichmann
H-Erich
HE
Illig
Thomas
T
Döring
Frank
F
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013045:Species Specificity; D055105:Waist Circumference
D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein; D002784:Cholesterol